Hippocalcin-like protein 1 (HPCAL1)

Hippocalcin-like protein 1 (HPCAL1) is a neuron-specific calcium-binding protein, primarily expressed in the retina and brain, and belongs to the neuronal calcium sensor (NCS) protein family with EF-hand domains[2][3][1][5][6]. It closely resembles hippocalcin and is nearly identical in sequence to the rat and mouse homologs. HPCAL1 participates in calcium-dependent signal transduction and phototransduction, potentially influencing rhodopsin phosphorylation in the retina and contributing to neuronal signaling in the central nervous system[2][3][5][6]. Recent research implicates HPCAL1 in multiple disease roles: it acts as a tumor suppressor in hepatocellular carcinoma by stabilizing p21 and inhibiting cell cycle progression[1]; regulates neuronal differentiation (through PHOX2B interaction) with relevance in neuroblastoma pathogenesis[1]; and plays a unique role as an autophagy receptor, selectively mediating CDH2 degradation to promote ferroptotic cell death—particularly relevant in tumor suppression and pancreatitis[4]. Its expression and DNA methylation status are emerging as potential biomarkers in disease, environmental exposure, and forensic tissue identification[1]. HPCAL1 has hundreds of reported protein interactions, including torsinA and CDH2, and may modulate oncogenic signaling via direct activation of DCLK1 kinase[1][4]. It is not yet a direct drug target in clinical therapeutics, but its central functions in calcium homeostasis, neuronal viability, and regulated cell death highlight potential therapeutic relevance[1][4][5][6][7].

Other names

Hippocalcin-like protein 1HPCAL1VILIP-3BDR1HLP2Visinin-like protein 3Calcium-binding protein BDR-1

Promotes ferroptosis by mediating selective autophagic degradation of cadherin-2 (CDH2); stabilizes p21 to suppress cell cycle progression in cancer[1][4]; regulates calcium-dependent signaling pathways