Plin4, also known as perilipin 4, is a member of the perilipin family of lipid droplet proteins. These proteins play crucial roles in lipid droplet metabolism, with Plin4's function related to lipid droplet docking and potentially influencing processes such as lipolysis and lipid droplet maturation [4]. The long repetitive region of Plin4 sets it apart from other family members, and its expression is associated with lipid-related biological processes in various tissues [4].

In testicular Leydig cells, environmental stress increases Plin4 levels, which in turn exacerbates the decrease in testosterone levels by inducing ferroptosis. Plin4 siRNA can reverse environmental stress-induced lipid droplet deposition and ferroptosis in these cells [1]. In Parkinson's disease (PD) mouse models, neuronal SH2B1 promotes PLIN4 degradation. Sh2b1 deficiency exacerbates PD-related behavioral defects and neuronal apoptosis, while restoring neuron-specific Sh2b1 expression mitigates these effects by suppressing lipid peroxidation stress via the SH2B1-HSC70-PLIN4 axis [2]. In lipid metabolism studies, Senp7 deficiency impairs lipid droplet maturation in white adipose tissues by affecting Plin4 deSUMOylation, suggesting a role of Senp7 in promoting Plin4's lipid droplet localization [3].

In summary, Plin4 is important in lipid-related biological processes. Studies using mouse models, such as those related to ferroptosis in testicular Leydig cells, PD-related neurodegeneration, and lipid droplet maturation in adipose tissues, have revealed its role in specific disease-relevant biological processes. These findings contribute to understanding the mechanisms underlying male testosterone deficiency, Parkinson's disease, and lipid metabolism-related disorders [1,2,3].

References:

1. Zhang, Xu-Dong, Sun, Jian, Zheng, Xin-Mei, Xiong, Yong-Wei, Wang, Hua. 2024. Plin4 exacerbates cadmium-decreased testosterone level via inducing ferroptosis in testicular Leydig cells. In Redox biology, 76, 103312. doi:10.1016/j.redox.2024.103312. https://pubmed.ncbi.nlm.nih.gov/39173539/

2. Han, Xiaojuan, Liu, Yuan, Dai, Yan, Hu, Gang, Hu, Jun. 2022. Neuronal SH2B1 attenuates apoptosis in an MPTP mouse model of Parkinson's disease via promoting PLIN4 degradation. In Redox biology, 52, 102308. doi:10.1016/j.redox.2022.102308. https://pubmed.ncbi.nlm.nih.gov/35390677/

3. Pei, Jingwen, Zou, Dayuan, Li, Lu, Gao, Xiang, Lin, Zhaoyu. 2024. Senp7 deficiency impairs lipid droplets maturation in white adipose tissues via Plin4 deSUMOylation. In The Journal of biological chemistry, 300, 107319. doi:10.1016/j.jbc.2024.107319. https://pubmed.ncbi.nlm.nih.gov/38677512/

4. Griseti, Elena, Bello, Abdoul Akim, Bieth, Eric, Laurell, Henrik, Čopič, Alenka. 2024. Molecular mechanisms of perilipin protein function in lipid droplet metabolism. In FEBS letters, 598, 1170-1198. doi:10.1002/1873-3468.14792. https://pubmed.ncbi.nlm.nih.gov/38140813/