CABP1 (calcium binding protein 1) is a neuronal EF-hand calcium sensor protein that modulates voltage-gated calcium channel activity through competitive binding with calmodulin. The protein binds constitutively to Mg2+ at EF-1 with Kd ~300 μM and cooperatively to Ca2+ at EF-3 and EF-4 with Kd ~2.5 μM 1. CABP1 exhibits opposite effects to calmodulin on L-type calcium channels by binding to the same IQ domain: it prevents calcium-dependent inactivation (CDI) and promotes calcium-dependent facilitation (CDF), allowing sustained calcium influx 23. The mechanism involves direct competition between apo-state CABP1 and calmodulin for the channel IQ domain, with their relative binding affinities determining channel behavior 3. CABP1 also regulates voltage-dependent activation and inactivation through interactions with both N- and C-terminal domains of CaV1.2 channels 4. Additionally, CABP1 inhibits TRPC5 channels and modulates other calcium signaling pathways 5. The protein undergoes distinct conformational changes upon Ca2+ and Mg2+ binding, switching between structurally different states that serve distinct regulatory functions 16. Variants in CABP1 have been identified as potential candidates for human genetic disorders 7.