Tubby-like protein 3 (TULP3)

Tubby-like protein 3 (TULP3) is a member of the tubby gene family of bipartite transcription factors, identified in diverse species including plants and animals[5][4]. TULP3 functions primarily as an adaptor within the primary cilium, where it links the intraflagellar transport A (IFT-A) complex to plasma membrane phosphoinositides, regulating the trafficking and localization of G protein-coupled receptors (GPCRs) to the ciliary membrane[1][2]. It is also a negative regulator of Sonic hedgehog (Shh) signaling during embryonic development, notably by promoting the repression machinery of this pathway[3][5]. TULP3’s disruption in mice leads to neural tube and craniofacial malformations and is associated with excessive Shh pathway activation, indicating its essential role in neural development and ciliary signaling[3]. Elevated TULP3 expression has recently been implicated in cancer progression, particularly in pancreatic, colorectal, and non-small-cell lung cancers[4]. Biallelic TULP3 variants in humans can cause progressive fibrotic diseases affecting the liver, kidneys, and heart[4]. No drugs are known to directly target TULP3, and its primary biological role concerns intracellular protein trafficking rather than classical receptor, enzyme, or transporter functions[1][5].

Other names

Tubby-related protein 3TUBL3Tubby-like protein 3HRCDFtubby-related protein 3tubby like protein 3