The Caenorhabditis elegans PMR1, a P-type Ca2+/Mn2+ ATPase, is expressed in hypodermal seam cells, intestinal cells and spermatheca; localized in Golgi complex. Knock down of pmr-1 as well as overexpression of truncated Caenorhabditis elegans PMR1, which mimics dominant mutations observed in human Hailey-Hailey disease, renders the worm highly sensitive to EGTA and Mn2+. Interestingly, pmr-1 knock down not only causes animals to become resistant to oxidative stress but also suppresses high reactive oxygen species sensitivity of smf-3 RNA-mediated interference and daf-16 worms. These findings suggest that C. elegans PMR1 has important roles in Ca2+ and Mn2+ homeostasis and oxidative stress response.