TULP3, Tubby-like protein 3, is a member of the tubby family. It plays crucial roles in multiple biological processes, such as being essential for the trafficking of certain proteins to cilia, participating in cell regulation pathways like transcription and signal transduction [2,3,4,5,6]. It is associated with pathways like the TULP3-sirtuin-v-ATPase-AMPK pathway, which is activated by lithocholic acid (LCA) and can slow down ageing [1].

In gene knockout studies, embryonic-stage, nephron-specific Tulp3 knockout mice developed cystic kidneys with intact cilia, showing increased MAPK/ERK, mTOR, and cAMP signaling, suggesting its role in renal cystogenesis [2]. In another study, mice homozygous for a hypomorphic missense mutation in Tulp3 developed cysts at late embryonic stages, indicating its importance in regulating renal cystic disease [3]. Additionally, TULP3-knockout (KO) hTERT RPE-1 cells had downregulated ciliary formation and membrane-associated proteins ARL13B and INPP5E failed to localize to primary cilia [5].

In conclusion, Tulp3 is vital for protein trafficking to cilia and is involved in processes like ageing regulation and renal cystogenesis. The gene knockout mouse models have been instrumental in revealing its role in these disease-related biological processes, especially in understanding renal and hepatic fibrocystic diseases [1,2,3,7].