Mlph, also known as melanophilin, plays a crucial role in regulating skin pigmentation through the melanosome transport process. It acts as a linker between RAB27A and myosin Va during this process, and the MYO5A-MLPH-RAB27A ternary protein complex is essential for anchoring mature melanosomes in melanocytes for transfer to keratinocytes [4,6].

MLPH has been implicated in various disease-related processes. In pancreatic adenocarcinoma, MLPH regulates epithelial-mesenchymal transition (EMT) through the PI3K-AKT signaling pathway, influencing cell proliferation, invasion, and migration. High MLPH expression in rectal cancer patients correlates with a poorer response to preoperative chemoradiotherapy and reduced patient survival [3,7]. Also, in prostate cancer, although a retracted study once proposed that MLPH accelerates EMT, indicating its potential role in cancer progression [1,2]. In adipocytes, MLPH is a novel adipogenic factor that controls redox homeostasis to inhibit lipid peroxidation [5].

In conclusion, Mlph is essential for skin pigmentation through melanosome transport. Its role in diseases such as pancreatic, rectal, and potentially prostate cancer, as well as in adipocyte function, highlights its significance in multiple biological and disease-related processes. Studies on Mlph contribute to understanding disease mechanisms and may offer potential therapeutic targets.

References:

1. Zhang, Tianbiao, Sun, Yangyang, Zheng, Tao, Jia, Donghui, Zhang, Weixing. 2020. MLPH Accelerates the Epithelial-Mesenchymal Transition in Prostate Cancer. In OncoTargets and therapy, 13, 701-708. doi:10.2147/OTT.S225023. https://pubmed.ncbi.nlm.nih.gov/32158222/

2. . 2023. MLPH Accelerates the Epithelial-Mesenchymal Transition in Prostate Cancer [Retraction]. In OncoTargets and therapy, 16, 1051-1052. doi:10.2147/OTT.S454940. https://pubmed.ncbi.nlm.nih.gov/38116521/

3. Wei, Mengda, Yang, Xi, Yang, Xiaoying, Wei, Junren, Tian, Lei. 2024. MLPH regulates EMT in pancreatic adenocarcinoma through the PI3K-AKT signaling pathway. In Journal of Cancer, 15, 5828-5838. doi:10.7150/jca.94573. https://pubmed.ncbi.nlm.nih.gov/39308678/

4. Salah, Haneen T, Yang, Richard K, Roy-Chowdhuri, Sinchita, Nagarajan, Priyadharsini, Cho, Woo Cheal. 2024. Spitz melanocytic neoplasms with MLPH::ALK fusions: Report of two cases with previously unreported features and literature review. In Journal of cutaneous pathology, 51, 407-414. doi:10.1111/cup.14605. https://pubmed.ncbi.nlm.nih.gov/38444194/

5. Kim, Mi-Yeun, Kim, Yang-Hyun, Park, Eun-Ran, Lee, Kee-Ho, Shin, Hyun-Jin. 2024. MLPH is a novel adipogenic factor controlling redox homeostasis to inhibit lipid peroxidation in adipocytes. In Biochemical and biophysical research communications, 734, 150459. doi:10.1016/j.bbrc.2024.150459. https://pubmed.ncbi.nlm.nih.gov/39083977/

6. Huang, Qiaorong, Yuan, Yefeng, Gong, Juanjuan, Li, Wei, Wei, Aihua. 2022. Identification of a Novel MLPH Missense Mutation in a Chinese Griscelli Syndrome 3 Patient. In Frontiers in medicine, 9, 896943. doi:10.3389/fmed.2022.896943. https://pubmed.ncbi.nlm.nih.gov/35602484/

7. Li, Wan-Shan, Chen, Chih-I, Chen, Hsin-Pao, Tsai, Chia-Jen, Yang, Ching-Chieh. 2021. Overexpression of MLPH in Rectal Cancer Patients Correlates with a Poorer Response to Preoperative Chemoradiotherapy and Reduced Patient Survival. In Diagnostics (Basel, Switzerland), 11, . doi:10.3390/diagnostics11112132. https://pubmed.ncbi.nlm.nih.gov/34829479/