RALGAPB encodes the non-catalytic beta subunit of RalGAP complexes, which function as GTPase-activating proteins for Ral small GTPases (RALA and RALB) 1. As a scaffolding component, RALGAPB is essential for complex assembly and stability; loss of RalGAPB protein levels occurs when its catalytic partner RalGAPA1 is deficient, indicating interdependence of complex subunits 1. The RalGAP tetrameric architecture, stabilized by RALGAPB's unique domains, is required for in vivo function and acts as a tumor suppressor by negating oncogenic Ras signaling 2. Clinically, RALGAPB mutations are associated with neurodevelopmental disorders, particularly autism spectrum disorder and developmental delay. A genome-wide significant excess of de novo loss-of-function variants in RALGAPB has been identified in ASD and related conditions 3. RALGAPB disruption has also been implicated in infantile spasms and macrocephaly 45. Dysregulation of RalA signaling through RALGAPB deficiency affects neuronal function and brain development, potentially through alterations in cell-surface lipid raft components and anchorage-dependent cell signaling 1. Additionally, microexons within RALGAPB are required for correct timing of autism-linked gene expression during neurogenesis 6. RALGAPB represents an emerging component of the RALopathy disease spectrum, warranting consideration in clinical genetic diagnosis of neurodevelopmental disorders.