LAMB4 encodes laminin subunit beta-4, a critical extracellular matrix (ECM) component that mediates cell attachment, migration, and tissue organization during development 1. LAMB4 functions as part of laminin-443, a previously unreported laminin trimer containing laminin α4 and γ3 chains, and is necessary for actin filament accumulation 1. Mechanistically, LAMB4 is essential for peripheral sensory neuron (SN) development and survival; LAMB4 knockout impairs neural crest cell migration and SN development 1. LAMB4 localizes to the myenteric plexus of colonic tissue and regulates enteric nervous system development and function 2. Disease relevance is substantial. LAMB4 mutations occur in 11.8% of gastric cancers and 7.6% of colorectal cancers with microsatellite instability (MSI-H), with loss of LAMB4 expression in 17-32% of these cancers 3. Rare LAMB4 variants segregate with familial diverticulitis and reduce LAMB4 protein levels, potentially contributing to colonic dysmotility 2. In Familial Dysautonomia, LAMB4 variants downregulate expression and contribute to peripheral nervous system defects 1. LAMB4 variants are also identified in primary myelofibrosis 4 and myelodysplastic syndrome, showing prognostic significance 5. High LAMB4 expression correlates with poor prognosis in head and neck squamous cell carcinoma and glioma [PMID:36081907; 65]. Clinically, LAMB4 represents a novel biomarker for cancer prognosis and potential therapeutic target for nervous system disorders.