EFHB (EF-hand domain family member B, also known as CFAP21) functions as a dual-role protein with roles in calcium signaling and ciliary motility. As a cytosolic calcium sensor, EFHB modulates store-operated calcium entry (SOCE) by interacting with STIM1 upon endoplasmic reticulum store depletion in a calcium-dependent manner 1. This interaction regulates the STIM1-SARAF complex dynamics, controlling Orai1 channel activation and subsequent slow calcium-dependent inactivation, ultimately facilitating NFAT translocation from cytosol to nucleus 1. Additionally, EFHB serves as a microtubule inner protein (MIP) component of dynein-decorated doublet microtubules in the ciliary axoneme, contributing to motile cilia beating. In the male germline, EFHB is a sperm flagellar protein whose abnormal abundance is associated with male infertility phenotypes including oligozoospermia and oligoasthenoteratozoospermia 2, suggesting its importance for sperm motility and flagellar function. While EFHB was examined as a candidate gene in type 1 diabetes genetics studies, no significant association was established 3. The protein's dual localization and function in calcium signaling and axonemal structures position it as a key regulator at the intersection of cellular motility and immunoregulatory calcium signaling.