Hippocalcin (HPCA)

Hippocalcin is a neuron-specific calcium-binding protein of the neuronal calcium sensor (NCS) family, encoded by the HPCA gene and predominantly expressed in the hippocampus and other brain regions[4][5]. It features EF-hand motifs for calcium binding and a myristoyl switch, allowing reversible membrane association in response to Ca²⁺[1][4]. Hippocalcin modulates voltage-dependent calcium channel activity, shapes neuronal afterhyperpolarization, regulates synaptic plasticity, and is critical for memory formation and neuroprotection[1][2][5]. By promoting efficient calcium extrusion, it guards against cell death induced by excitotoxic or oxidative stress. It also governs astrocytic differentiation and glial cell development through STAT3 signaling[3]. Mutations in HPCA can cause movement disorders such as dystonia, likely through disruption of calcium signaling and neuronal excitability[2]. HPCA interacts with other neuronal regulators such as NAIP, MLK2, and PLD2, influencing pathways linked to cell survival and synaptic modulation[1][5]. Currently, there are no drugs developed specifically to target HPCA, but its levels can be modulated by some neuroprotective compounds, making it a potential disease marker or therapeutic adjunct in neurodegenerative diseases.

Other names

Neuron-specific calcium-binding protein hippocalcinBDR2Calcium-binding protein BDR-2DYT2dystonia 2, torsion (autosomal recessive)

Neuroprotective agents can upregulate HPCA, supporting neuron survival and attenuating calcium-induced toxicity[1]