TTC1 (tetratricopeptide repeat domain 1) is a multifunctional adapter protein with roles in both cellular signaling and protein homeostasis. In signal transduction, TTC1 acts downstream of GNA15 to stimulate Ras/ERK1/2 phosphorylation independently of phospholipase Cβ signaling 12. Mechanistically, TTC1 interacts with GNA15 and SOS2 to form a macromolecular signaling complex with high affinity for HRAS 3, and participates in signaling via GNA14, activating NF-κB through Ras/ERK pathways 4. Beyond signaling, TTC1 supports protein homeostasis by cooperating with HSP40 in the HSP70 chaperone cycle, promoting protein folding through regulated dissociation of the inhibitor HSPBP1 5. Clinically, rare homozygous TTC1 variants (p.Phe262Val) are associated with pontocerebellar hypoplasia and periventricular leukomalacia 6, representing the first implication of TTC1 in congenital brain malformations. TTC1 is also upregulated in hepatocellular carcinoma and promotes HCC progression through MAPK/ERK pathway activation when interacting with PGRP-S 7. Common variants in TTC1 associate with multidimensional sleep health metrics 8, and genetic associations link TTC1 to mood disorders 9.