CYRIA (CYFIP-related Rac1 interactor A) is a negative regulator of RAC1 signaling that controls actin-based cell protrusions and migration. CYRIA binds activated RAC1 through a conserved DUF1394 domain and acts as a 'local inhibitor' by suppressing Scar/WAVE complex-mediated actin polymerization 1. This inhibitory mechanism restricts protrusion size and duration; CYRIA-depleted cells exhibit broader lamellipodia with prolonged pseudopods, while CYRIA overexpression produces short-lived, unproductive protrusions 1. Beyond protrusion control, CYRIA-A regulates macropinosome formation and integrin trafficking; CYRIA depletion enhances migration, invasion, and anchorage-independent growth 2. Structurally, CYRIA proteins form autoinhibited homo- and heterodimers that provide additional regulatory layers for RAC1 signaling 3. Clinically, CYRIA variants are associated with non-syndromic orofacial clefts (NSOFCs), a common craniofacial birth defect. Multiple GWAS and replication studies have identified CYRIA SNPs (rs7552, rs3821949, rs3917201) as contributing risk factors for NSOFCs across different populations 456. Additionally, a CYRIA variant (rs12613255) shows significant association with developmental stuttering 7. These findings establish CYRIA as functionally important for craniofacial and neural development.