HEPACAM encodes an immunoglobulin-like cell adhesion molecule that serves multiple critical functions in cellular regulation and neuroglial biology. The protein acts as a tumor suppressor, inhibiting cell proliferation through G1 phase arrest and promoting c-Myc protein degradation via post-transcriptional mechanisms 1. HEPACAM suppresses cell growth through an AMPK/mTOR-dependent pathway, activating AMPK while down-regulating mTOR and its downstream targets c-Myc and cyclin D1 2. The protein regulates cell motility and cell-matrix interactions, with its cytoplasmic domain being essential for these adhesive functions 34. In the nervous system, HEPACAM plays a crucial role in astrocyte self-organization and territorial coordination during development, regulating astrocyte competition for synaptic territory and gap junction coupling between astrocytes 5. Additionally, astrocyte-derived exosomal HEPACAM provides neuroprotective effects against excitotoxicity, though this protective function is disrupted by inflammatory cytokines in neurodegenerative conditions like ALS 6. Mutations in HEPACAM cause megalencephalic leukoencephalopathy with subcortical cysts, highlighting its importance in maintaining proper brain structure and function. The protein is frequently silenced in various cancers, supporting its role as a tumor suppressor.