{"id":42,"date":"2026-05-07T10:46:19","date_gmt":"2026-05-07T10:46:19","guid":{"rendered":"https:\/\/hcp.biomarin.com\/en-us\/cln2\/?page_id=42"},"modified":"2026-09-15T14:37:23","modified_gmt":"2026-09-15T14:37:23","slug":"pathophysiology","status":"publish","type":"page","link":"https:\/\/hcp.biomarin.com\/en-us\/cln2\/overview\/pathophysiology\/","title":{"rendered":"Pathophysiology"},"content":{"rendered":"<div id=\"acf-block-6a01a4996109f\" class=\"simple-hero\">\n        <div class=\"wrapper\">\n\t\t<div class=\"inner-wrapper\">\n\t\t\t<div class=\"hero-content\">\n\t\t\t\t\t\t\t\t    <span class=\"section-title\">Overview<\/span>\n\t\t\t\t\t\t\t\t\t\t\t\t    <h1>Pathophysiology\n<\/h1>\n\t\t\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t<\/div>\n<\/div>\n\n<figure id=\"acf-block-6a01a499612b8\">\n    <div class=\"image image-align-left\">\n                    <img decoding=\"async\" class=\"\" src=\"https:\/\/hcp.biomarin.com\/en-us\/cln2\/wp-content\/uploads\/sites\/3\/2026\/05\/NCL-disorders-hero.jpg?v=0.4\" alt=\"\" \/>            <\/div>\n    <\/figure>\n\n<div id=\"acf-block-6a01a499614d8\" class=\"block wrapped-content block-zero-bottom\">\n    <div class=\"wrapper\">\n        <div class=\"inner-wrapper\">\n                \n<div id=\"acf-block-6a01a4996161c\" class=\"block-wysiwyg\">\n            \n\n<h2 style=\"font-weight: bold\">TPP1 enzyme deficiency results in neurodegeneration in children with CLN2 disease<sup>1<\/sup><\/h2>\n\n\n    <\/div>\n        <\/div>\n    <\/div>\n<\/div>\n\n<div id=\"acf-block-6a01964375062\" class=\"block cards cards-3-col bg-band bg-band-white block-zero-top block-tight-bottom block-remove-top-padding block-remove-bottom-padding\">\n\t<div class=\"wrapper\">\n\t\t<div class=\"inner-wrapper\">\n\t\t\t<div class=\"cards-title\">\n\t\t\t    \t\t\t\t\t\t\t<\/div>\n\t\t\t<div class=\"cards-wrapper\">\n\t\t\t    \n<div id=\"acf-block-6a019643755e9\" class=\"card card-inner-image card-inner-image-large\" data-muted-autoplay=\"false\">\n        <div class=\"card-content\">\n                    <img decoding=\"async\" class=\"\" src=\"https:\/\/hcp.biomarin.com\/en-us\/cln2\/wp-content\/uploads\/sites\/3\/2026\/05\/Pathophy-1-1.png?v=0.4\" alt=\"\" \/>                \n                                                                                                            <p>Pathogenic variants in the <em>CLN2\/TPP1<\/em> gene result in deficient activity of the tripeptidyl\u00ad\u2010peptidase 1 (TPP1) enzyme. TPP1 is a protease that cleaves N-terminal tripeptides from substrates in lysosomes.<sup>1,2<\/sup><\/p>\n                                                                                    <\/div>\n<\/div>\n\n<div id=\"acf-block-6a01964375685\" class=\"card card-inner-image card-inner-image-large\" data-muted-autoplay=\"false\">\n        <div class=\"card-content\">\n                    <img decoding=\"async\" class=\"\" src=\"https:\/\/hcp.biomarin.com\/en-us\/cln2\/wp-content\/uploads\/sites\/3\/2026\/05\/Pathophy-2.png?v=0.4\" alt=\"\" \/>                \n                                                                                                            <p>The absence or reduced activity of the TPP1 enzyme is associated with an accumulation of lysosomal autofluroescent lipopigment storage material.<sup>2,3<\/sup><\/p>\n                                                                                    <\/div>\n<\/div>\n\n<div id=\"acf-block-6a01964375708\" class=\"card card-inner-image card-inner-image-large\" data-muted-autoplay=\"false\">\n        <div class=\"card-content\">\n                    <img decoding=\"async\" class=\"\" src=\"https:\/\/hcp.biomarin.com\/en-us\/cln2\/wp-content\/uploads\/sites\/3\/2026\/05\/Pathophy-3.png?v=0.4\" alt=\"\" \/>                \n                                                                                                            <p>Over time, cell dysfunction, cell death, and atrophy occur.<sup>3,4<\/sup><\/p>\n                                                                                    <\/div>\n<\/div>\n\t\t\t<\/div>\n\t\t<\/div>\n\t<\/div>\n<\/div>\n\n<div id=\"acf-block-6a01a49961a54\" class=\"block boxed-content block-zero-top\">\n\t<div class=\"wrapper\">\n\t\t<div class=\"inner-wrapper\">\n\t\t\t<div class=\"box\">\n\t\t\t\t                    <h2>Continuous accumulation of lysosomal storage materials causes cell death and result in neurodegeneration and noticeable symptoms of CLN2 disease.\n<\/h2>\n                \t\t\t\t\t\t\t<\/div>\n\t\t<\/div>\n\t<\/div>\n<\/div>\n\n<div id=\"acf-block-6a01a944bfcc7\" class=\"block references\">\n    <div class=\"wrapper\">\n\t\t<div class=\"inner-wrapper\">\n\t\t    \t\t\t    <h4>References:\n<\/h4>\n\t\t\t\t\t\t                <ol>\n                                                                                                                        <li><span>Schulz A, Kohlsch\u00fctter A, Mink J, Simonati A, Williams R. NCL diseases \u2013 clinical perspectives. <em>Biochimica et Biophysica Acta.<\/em> 2013;1832:1801-1806\n<\/span><\/li>\n                                                                                                                                                <li><span>Mole SE, Williams RE, and Goebel HH. Correlations between genotype, ultrastructural morphology and clinical phenotype in the neuronal ceroid lipofuscinoses. <em>Neurogenetics.<\/em>2005;6:107-126.\n<\/span><\/li>\n                                                                                                                                                <li><span>Chang M, Cooper JD, Davidson BL, et al. CLN2. In: Mole S, Williams R, and Goebel H, eds. <em>The neuronal ceroid lipofuscinoses (Batten Disease)<\/em>. 2nd ed. Oxford, United Kingdom: Oxford University Press; 2011:80-109.\n<\/span><\/li>\n                                                                                                                                                <li><span>Haltia M. The neuronal ceroid-lipofuscinoses: from past to present. <em>Biochimica et Biophysica Acta.<\/em>2006;1762:850-856.\n<\/span><\/li>\n                                                            <\/ol>\n\t\t\t\t\t<\/div>\n\t<\/div>\n<\/div>","protected":false},"excerpt":{"rendered":"","protected":false},"author":2,"featured_media":0,"parent":36,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"","meta":{"_acf_changed":false,"inline_featured_image":false,"footnotes":""},"class_list":["post-42","page","type-page","status-publish","hentry"],"acf":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v28.2 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>CLN2 Connection | Pathophysiology | HCP BioMarin<\/title>\n<meta name=\"description\" content=\"Explore the pathophysiology of CLN2 disease, including TPP1 enzyme deficiency, lysosomal dysfunction and the progressive loss of neuronal function.\" \/>\n<meta name=\"robots\" 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