Department of Pharmacy, Shanghai Sixth People's Hospital Affiliated Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China.
Department of Critical Care Medicine, Shanghai Sixth People's Hospital Affiliated Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China.
Biomed Pharmacother. 2024 Sep;178:117237. doi: 10.1016/j.biopha.2024.117237. Epub 2024 Aug 2.
The Lysosomal Protein Transmembrane 5 (LAPTM5) is a lysosomal transmembrane protein preferentially expressed in hematopoietic cells. The human LAPTM5 gene is located at position 1p34 and extends approximately 25 kb. Its protein includes five transmembrane domains, three PY motifs, and one UIM. The PY and UIM motifs can interact with various substrates, mediating sorting of proteins from Golgi to lysosome and subsequently participating in intracellular substrate transport and lysosomal stability regulation. Overexpression of LAPTM5 can induce lysosomal cell death (LCD), although the integrity of LAPTM5 protein is necessary for maintaining lysosome stability. Furthermore, LAPTM5 plays a role in autophagy activation during disease processes and has been confirmed to be closely associated with the regulation of immunity and inflammation. Therefore, LAPTM5 regulates a wide range of physiological processes and is involved in various diseases. This article summarizes the characteristics of the LAPTM5 gene and protein structure and provides a comprehensive review of the mechanisms involved in cell death, autophagy, immunity, and inflammation regulation. It emphasizes the significance of LAPTM5 in the clinical prevention and treatment of cardiovascular diseases, immune system disorders, viral infections, cancer, and other diseases, which could provide new therapeutic ideas and targets for human diseases.
溶酶体跨膜蛋白 5（LAPTM5）是一种优先在造血细胞中表达的溶酶体跨膜蛋白。人类 LAPTM5 基因位于 1p34 位置，大约 25kb 长。其蛋白包含五个跨膜结构域、三个 PY 基序和一个 UIM。PY 和 UIM 基序可以与各种底物相互作用，介导蛋白质从高尔基体到溶酶体的分拣，随后参与细胞内底物运输和溶酶体稳定性调节。LAPTM5 的过表达可诱导溶酶体细胞死亡（LCD），尽管 LAPTM5 蛋白的完整性对于维持溶酶体稳定性是必要的。此外，LAPTM5 在疾病过程中参与自噬的激活，并已被证实与免疫和炎症的调节密切相关。因此，LAPTM5 调节广泛的生理过程并参与各种疾病。本文总结了 LAPTM5 基因和蛋白结构的特征，并对细胞死亡、自噬、免疫和炎症调节的相关机制进行了全面综述。强调了 LAPTM5 在心血管疾病、免疫系统紊乱、病毒感染、癌症等疾病的临床预防和治疗中的重要性，为人类疾病的治疗提供了新的思路和靶点。
