FRMD5 (FERM domain containing 5) is a scaffolding protein that plays critical roles in neurodevelopment and cell motility regulation. The protein localizes at cell adherens junctions where it stabilizes cell-cell contacts and regulates cell-matrix interactions through binding to integrin β5 subunit 1. FRMD5 inhibits cell migration by promoting cell-matrix adhesion and cell spreading on vitronectin, while also interacting with ROCK1 kinase to inhibit myosin light chain phosphorylation and actin stress fiber formation 1. In neurodevelopment, FRMD5 is essential for proper neuronal morphology and synaptic function, with deficiency leading to learning and memory dysfunction, impaired social function, and repetitive behaviors in mouse models 2. The protein is also a direct transcriptional target of the β-catenin/TCF7L2 complex, linking it to Wnt signaling pathways 3. Clinically, de novo heterozygous missense variants in FRMD5 cause a neurodevelopmental disorder characterized by developmental delay, intellectual disability, childhood-onset ataxia, abnormal eye movements including nystagmus, and seizures 45. Functional studies demonstrate that pathogenic variants behave as partial loss-of-function or dominant-negative alleles, supporting FRMD5's intolerance to functional disruption 4. These findings establish FRMD5 as an important regulator of both cellular adhesion and neurological development.