GPSM2 (G protein signaling modulator 2) is a critical regulator of cell division and polarity with primary functions in mitotic spindle organization and G protein signaling. It plays a central role in orienting the mitotic spindle via interaction with NUMA1 and recruitment of the cortical dynein-dynactin complex during metaphase, facilitating asymmetric cell divisions 12. GPSM2 functions as a guanine nucleotide dissociation inhibitor for Gαi proteins and localizes to stereocilia tips in hair cells, where it partners with GNAI3, MYO15A, and WHRN to specify tallest stereocilia and promote actin dynamics 34. Mutations in GPSM2 cause Chudley-McCullough syndrome, an autosomal recessive disorder characterized by sensorineural hearing loss and brain malformations including polymicrogyria and corpus callosum agenesis, reflecting defective asymmetric cell divisions during development 53. The GoLoco motifs are essential for hearing function and proper kinocilium positioning 6. Beyond genetic disease, GPSM2 dysregulation has emerging roles in cancer progression; reduced GPSM2 expression promotes lung adenocarcinoma proliferation via EGFR signaling 7. Additionally, truncated GPSM2 isoforms are upregulated in systemic lupus erythematosus CD4+ T cells, promoting migration and potentially contributing to organ infiltration 8. GPSM2 represents both a diagnostic/prognostic biomarker and potential therapeutic target across multiple disease contexts 9.