Von Willebrand factor type A and cache domain-containing protein 1 (CACHD1)

Von Willebrand factor type A and cache domain-containing protein 1 (CACHD1) is a single-pass transmembrane glycoprotein identified as an α2δ-like auxiliary subunit that regulates the function and cell surface expression of certain voltage-gated calcium channels, including T-type (Cav3.x) and N-type (Cav2.2) channels[1][3][4][5]. It contains two extracellular cache domains—structural motifs usually found in bacterial chemosensors—and a von Willebrand factor type A (VWFA) domain featuring a variant MIDAS motif, features it shares with canonical α2δ channel subunits[2][3]. CACHD1 is involved in neuronal signaling and calcium ion homeostasis in the central and peripheral nervous systems, with strong implications in auditory and vestibular biology as shown by hearing loss and balance defects in knockout mouse models[4]. While its direct association with specific human diseases is still being studied, its modulation of calcium channel function suggests potential involvement in sensory disorders, pain, epilepsy, and perhaps metabolic traits[1][3][4]. CACHD1 remains a candidate for future therapeutic targeting, notably as an alternative to more directly modulating channel pore-forming subunits or for fine-tuned control of neuronal excitability[3][4].

Other names

CACHD1VWCD1KIAA1573Cache domain-containing protein 1VWFA and cache domain-containing protein 1von Willebrand factor type A and cache domain containing 1

Modulation of voltage-gated calcium channel open probability and surface expression; increases T-type (Cav3.x) and N-type (Cav2.2) calcium currents, competes with canonical α2δ subunits for channel modulation