TPRG1L (tumor protein p63 regulated 1 like) is a presynaptic protein involved in synaptic transmission regulation. At the molecular level, TPRG1L functions as a presynaptic protein that decreases calcium sensitivity of neurotransmitter release, thereby modulating synaptic release probability [UniProt annotation]. The protein localizes to presynaptic terminals including the calyx of Held and colocalizes with presynaptic markers in hippocampal mossy fiber terminals and cerebellar inhibitory terminals 1. Beyond its synaptic role, TPRG1L functions as an upstream regulator of NF-κB-dependent inflammatory signaling. TPRG1L upregulates IL-6 expression through NF-κB pathway activation 2, and is transcriptionally regulated by TERC through RNA-DNA triplex formation 3. TPRG1L expression is elevated in inflammation-related diseases including type II diabetes and multiple sclerosis 3. Clinically, TPRG1L shows relevance to multiple pathologies. In gallbladder cancer, TPRG1L overexpression promotes cell proliferation through NF-κB activation, and its inhibition by tRF-3013b suppresses tumor growth 4. Additionally, TPRG1L is identified as a candidate gene associated with multisite chr1 pain in depression patients 5. These findings suggest TPRG1L as a potential therapeutic target for inflammatory diseases and certain malignancies.