TAC4 encodes tachykinin precursor 4, which produces several bioactive peptides including hemokinin-1 (HK-1) and endokinins that bind to tachykinin NK1 receptors with similar potency to substance P 1. The gene demonstrates widespread expression in immune cells, nervous system regions including the hypothalamic-pituitary-adrenal axis, hippocampus, and amygdala, as well as in peripheral tissues like bronchi and lung parenchyma 23. TAC4-derived peptides function as mediators of pain transmission, stress responses, and airway smooth muscle contraction 23. Mechanistically, these peptides activate NK1 and NK2 receptors, with HK-1 showing distinct signaling pathways from substance P despite structural similarities 4. TAC4 has clinical relevance in multiple contexts: genetic variants associate with forearm fracture susceptibility, with Tac4-/- mice showing reduced mechanical bone strength 5; the gene serves as a prognostic biomarker in osteosarcoma, correlating with tumor microenvironment characteristics 6; and HK-1 mediates chr17 stress-induced pain, particularly mechanical hyperalgesia 2. The peptides also cause airway smooth muscle contraction in humans and guinea pigs, suggesting potential roles in respiratory pathophysiology 3.