HMCN1 (hemicentin 1) is an extracellular matrix protein involved in basement membrane organization and cell adhesion. Mechanistically, HMCN1 regulates podocyte cytoskeletal dynamics through TGF-β signaling, promoting F-actin reduction and podocyte morphological changes 1. HMCN1 physically interacts with keratin 14 (K14) and contributes to basement membrane zone (BMZ) stability; deleterious HMCN1 variants aggravate epidermolysis bullosa simplex severity by disrupting protein stability and reducing keratin intermediate filament formation 2. HMCN1 can be cleaved by ADAMTS12 metalloprotease, enabling activation of injury-responsive fibroblasts with aberrant JAK/STAT signaling during fibrogenesis 3. In cancer biology, HMCN1 mutations associate with altered tumor immunity and metabolism pathways in clear cell renal carcinoma 4, while elevated HMCN1 expression in cancer-associated fibroblasts promotes ovarian carcinoma invasiveness via RhoA signaling 5. HMCN1 mutations correlate with poor prognosis in rectal neuroendocrine tumors 6. Clinically, HMCN1 represents a genetic modifier influencing disease severity in inherited blistering disorders and a potential biomarker for cancer prognosis and immune microenvironment composition.