IL1RAPL2 is an X-linked gene encoding an interleukin-1 receptor accessory protein-like molecule specifically expressed in the central nervous system 1. The protein localizes to the plasma membrane and functions in glutamatergic synapses, regulating presynapse assembly and participating in cell surface receptor signaling [GO annotations]. IL1RAPL2 shares 70.4% similarity with IL1RAPL1, a calcium-regulated gene implicated in vesicle release and dendrite differentiation 1. IL1RAPL2 is implicated in neurodevelopmental disorders. It was identified as a candidate gene for X-linked mental retardation (XLMR) 1 and has been investigated in autism spectrum disorders, though direct mutations in IL1RAPL2 have not been definitively established as causative 23. Notably, IL1RAPL2 was identified as a key gene marker for retinal ganglion cell development during fetal retina development 4. Beyond neurodevelopment, IL1RAPL2 demonstrates broader disease relevance. It was identified as a differential biomarker associated with cortical brain aging and expression correlated with aging status in plasma proteome studies 5. Additionally, IL1RAPL2 expression is altered in esophageal squamous cell carcinoma 6 and melanoma metastasis 7, with significant downregulation observed in cutaneous melanoma metastases. GRPR signaling in colorectal cancer can affect IL1RAPL2 expression 8, suggesting roles in cancer biology.