RAB40AL is an X-linked gene encoding a small Ras-like GTPase protein with a suppressor of cytokine signalling box domain 1. As a member of the Rab40 subfamily, RAB40AL functions as a substrate-recognition component of E3 ubiquitin ligase complexes mediating proteasomal degradation of target proteins, and participates in intracellular membrane trafficking regulation, including vesicle formation, movement, tethering, and fusion 2. The protein localizes to the cytoplasm and mitochondria, with expression detected in fetal and adult brain, kidney, lung, heart, liver, and skeletal muscle 1. RAB40AL is notable for being a primate innovation with no orthologues in lower vertebrates 1. Regarding disease relevance, while RAB40AL mutations were initially reported in Martin-Probst syndrome (MPS), an X-linked neurodevelopmental disorder featuring cognitive impairment, sensorineural hearing loss, and craniofacial anomalies 1, subsequent large-scale population studies have questioned this association 34. The p.D59G variant occurs at high frequency (2.47-2.86%) in asymptomatic control populations, suggesting it represents common genetic variation rather than disease causation 34. Additionally, RAB40AL was identified near a susceptibility locus (Xq22.1) for hepatitis B virus-related hepatocellular carcinoma, though NXF3, not RAB40AL, showed differential expression in HCC tissues 5. RAB40AL was also upregulated in lung cancer cells exposed to nitric oxide 6, and X-chromosome X involving RAB40AL have been associated with mental retardation 7.