MTSS2 is a membrane-deforming cytoskeletal regulator encoding an I-BAR domain protein (also called ABBA/MTSS1L) highly expressed in the central nervous system with critical roles in neurodevelopment and cell dynamics. Functionally, MTSS2 promotes plasma membrane dynamics by activating the small GTPase Rac1, potentiating PDGF-mediated formation of membrane ruffles and lamellipodia in fibroblasts 1. The protein localizes to edges of membrane protrusions and facilitates dendritic spine formation, particularly in GABAergic inhibitory neurons such as parvalbumin-positive interneurons 2. During neurogenesis, MTSS2 localizes to the cleavage furrow where it recruits the scaffolding protein Nedd9 and positively regulates RhoA activity, ensuring proper mitotic progression in neuronal progenitor cells 3. MTSS2 dysfunction causes intellectual developmental disorder with ocular anomalies and distinctive facial features (OMIM#620086), predominantly caused by the recurrent de novo variant c.2011C>T (p.Arg671Trp) 4. This variant functions as a partial loss-of-function and dominant-negative allele, impairing Rac1 activation and synaptic transmission 4. Clinical manifestations include developmental delay, mild intellectual disability, microcephaly, facial dysmorphisms, seizures, hypotonia, learning disabilities, and multisystem involvement including cardiac and renal anomalies 56. MTSS2 represents a predominantly neurological but multisystem disorder affecting cognitive development and neural function.