HPCAL4 (hippocalcin-like 4) is a neuronal calcium sensor protein involved in synaptic regulation and signal transduction. The protein mediates calcium-dependent processes, particularly in presynaptic vesicle cycling and neurotransmitter release 1. HPCAL4 is induced during fear conditioning in the lateral amygdala, where it functions alongside other synaptic proteins to regulate long-term associative memory formation 1. The gene is subject to transcriptional regulation by nuclear respiratory factor-1 (NRF-1) across the visinin-like subfamily of neuronal calcium sensors 2. In the context of aging, HPCAL4 was identified as an age-related gene whose knockdown in glioma cells affects cellular senescence, suggesting involvement in aging-associated processes 3. HPCAL4 expression is markedly upregulated in response to nicotine stress (4.71-fold) in normal breast epithelial cells, potentially linking it to cancer development 4. The protein also serves as a target for pathogenic bacterial effectors, being recognized by enterohemorrhagic E. coli translocated intimin receptor 5. In glioblastoma, HPCAL4 is identified as a core gene in ionic signaling-related pathways and demonstrates prognostic significance for patient survival 6. These findings indicate HPCAL4 plays multifaceted roles in neuronal function, cellular stress responses, and disease pathogenesis.