TMEM100 is a transmembrane protein with dual roles in vascular development and nociception. During embryonic vascular development, TMEM100 functions downstream of BMP9/BMP10-ALK1 signaling to promote arterial endothelium differentiation and vascular morphogenesis; Tmem100 null mice exhibit embryonic lethality with impaired endothelial differentiation and defective vasculogenesis 1. In the nervous system, TMEM100 modulates pain signaling by weakening the inhibitory interaction between TRPA1 and TRPV1 channels in dorsal root ganglia neurons, thereby increasing TRPA1 activity and potentiating inflammatory mechanical hyperalgesia 2. TMEM100 is expressed in enteric neurons throughout the gastrointestinal tract and co-localizes with the pan-neuronal marker PGP9.5 3, suggesting developmental roles in enteric nervous system differentiation. In cardiac tissue, TMEM100 acts as a TAK1 receptor that suppresses pathological cardiac hypertrophy by inhibiting TAK1-JNK/p38 signaling 4. Clinically, TMEM100 expression is downregulated in multiple cancers including lung adenocarcinoma, gastric cancer, and non-small cell lung cancer, where it functions as a tumor suppressor inhibiting metastasis and enhancing chemotherapy sensitivity 567. These findings position TMEM100 as a multifunctional regulator relevant to developmental, neurological, cardiac, and oncological processes.