CWH43 is a lipid remodeling enzyme involved in GPI-anchor maturation 1 that localizes to the endoplasmic reticulum and participates in glycosylphosphatidylinositol anchor biosynthesis. Mechanistically, CWH43 modifies the lipid anchors of GPI-anchored proteins, enabling their proper localization to cell membranes 1. Loss-of-function CWH43 variants have significant neurological implications: heterozygous deletions were identified in 10-15% of idiopathic normal pressure hydrocephalus (iNPH) patients in initial US cohorts 1, though subsequent population-scale studies in Finnish and Norwegian cohorts revealed lower prevalence (2.9-5.2%) with minimal disease risk effect 2. Mechanistically, CWH43 deletions decrease N-glycosylation of L1CAM, a critical neuronal cell adhesion molecule, reducing its membrane stability and increasing plasmin-mediated proteolytic cleavage 3. This leads to increased L1CAM shedding in cerebrospinal fluid and impaired intracellular signaling, particularly in ventricular zones where CWH43 is highly expressed 3. Beyond neurology, CWH43 functions as a tumor suppressor in colorectal cancer, with reduced expression correlating with poor prognosis 4. CWH43 suppression promotes epithelial-mesenchymal transition and cell proliferation via increased TTK-mediated cell cycle activity 4. CWH43 has also been identified as a diagnostic biomarker in ulcerative colitis 5.