NTRK1 encodes TrkA, a receptor tyrosine kinase that plays critical roles in nervous system development and nociception. The receptor mediates nerve growth factor (NGF) signaling through interaction with co-receptor neuropilin-1 (NRP1), which enhances TrkA trafficking to the plasma membrane and signaling endosomes 1. TrkA activation triggers downstream pathways including ERK/MAPK cascades and promotes neuronal development and pain signaling 1. Loss-of-function mutations in NTRK1 cause congenital insensitivity to pain with anhidrosis (CIPA), demonstrating its essential role in pain perception 2. In cancer, NTRK1 gene fusions create constitutively active oncoproteins that drive tumor growth across diverse solid tumors including lung cancer, colorectal cancer, and various sarcomas 34. These fusion proteins, such as IRF2BP2-NTRK1 and TPM3-NTRK1, are found in histiocytic neoplasms and other malignancies 56. TrkA can also promote cancer progression through phosphorylation-mediated regulation of cellular proteins like AGPS 7. The clinical significance of NTRK1 alterations has led to the development of TRK inhibitors like entrectinib and larotrectinib, which show therapeutic efficacy in NTRK-fusion positive cancers 34.