PHYHIPL, or phytanoyl-CoA hydroxylase-interacting protein-like, has an as-yet-unclear function, but its expression is altered in global ischemia, glioblastoma multiforme, and other conditions [1,2]. Bioinformatics analysis indicates it may be involved in pathways such as the TNF signaling pathway, the IL-17 signaling pathway, retrograde endocannabinoid signaling, and the cAMP signaling pathway, and may play a role in cell metabolism [2]. Genetic models can be valuable in further exploring its function.

Knock-in mice with the Ser19Stop SNP of PHYHIPL were generated. The results showed that PHYHIPL impacts the morphology of cerebellar Purkinje cells (PCs), the innervation of climbing fibers to PCs, the inhibitory inputs to PCs from molecular layer interneurons, and motor learning ability. This suggests that the Ser19Stop SNP of the PHYHIPL gene may be associated with cerebellum-related diseases [1].

In summary, while the exact function of PHYHIPL is still being elucidated, model-based research, especially the Ser19Stop knock-in mouse model, has revealed its significance in cerebellar-related biological processes and potential associations with cerebellum-related diseases.

References:

1. Sugimoto, Hisako, Horii, Takuro, Hirota, Jun-Na, Furuichi, Teiichi, Sadakata, Tetsushi. 2021. The Ser19Stop single nucleotide polymorphism (SNP) of human PHYHIPL affects the cerebellum in mice. In Molecular brain, 14, 52. doi:10.1186/s13041-021-00766-x. https://pubmed.ncbi.nlm.nih.gov/33712038/

2. Fu, HuangDe, Ge, Bin, Chen, DuanKai, Zheng, ChuanHua, Tang, QianLi. 2019. Phytanoyl-CoA 2-Hydroxylase-Interacting Protein-Like Gene Is a Therapeutic Target Gene for Glioblastoma Multiforme. In Medical science monitor : international medical journal of experimental and clinical research, 25, 2583-2590. doi:10.12659/MSM.913895. https://pubmed.ncbi.nlm.nih.gov/30962415/