HEBP1 (heme binding protein 1) is a mitochondrial-associated protein that binds heme and porphyrins with high affinity, facilitating removal of potentially toxic porphyrinogens from cells. Beyond its canonical heme-binding function, HEBP1 has emerged as a critical regulator of cellular homeostasis and disease pathogenesis. Mechanistically, HEBP1 modulates mitochondrial dynamics and vascular permeability through regulation of claudin family proteins 1. In pathological contexts, HEBP1 acts downstream of amyloid-beta and heme to promote neuronal apoptosis 2, contributing to neuronal loss in Alzheimer's disease, while deletion of HEBP1 protects neurons from heme- and Aβ-induced cell death 2. Additionally, HEBP1 cleavage generates F2L, a fragment with modulatory effects on inflammation 2. Clinically, HEBP1 demonstrates therapeutic potential in peripheral nerve injury and metabolic disease. Pericyte-derived HEBP1 delivered via extracellular vesicles promotes neurovascular regeneration and improves erectile function in cavernous nerve injury models 1. In diabetic conditions, HEBP1 enhances endothelial cell angiogenesis by reducing reactive oxygen species and activating the PI3K/AKT/eNOS signaling pathway 3, improving erectile function in diabetic mice. These findings position HEBP1 as both a pathogenic mediator in neurodegeneration and a therapeutic target for vascular and regenerative medicine applications.