RMDN3 (regulator of microtubule dynamics 3) functions as a critical tethering protein that facilitates communication between the endoplasmic reticulum (ER) and mitochondria. The protein localizes to the mitochondrial outer membrane and forms part of the VAPB-PTPIP51 tethering complex, where RMDN3 is also known as PTPIP51 1. This tethering function is essential for maintaining mitochondria-associated membranes (MAMs) that regulate calcium homeostasis, lipid metabolism, and cellular survival pathways 2. Under oxidative stress conditions, RMDN3 undergoes phosphorylation that enhances ER-mitochondria contacts and enables the transfer of lipid radicals from mitochondria to the ER, thereby reducing mitochondrial oxidative damage and preventing cell death 3. The VAPB-PTPIP51 interaction also regulates autophagy by controlling calcium delivery from ER stores to mitochondria 4. Disruption of RMDN3/PTPIP51 function has clinical significance in neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, frontotemporal dementia, and amyotrophic lateral sclerosis, where impaired ER-mitochondria signaling contributes to disease pathology 5. Additionally, RMDN3 has been implicated in melanoma susceptibility and early embryonic development 67.