Mutations in the E3 ubiquitin ligase parkin cause early‐onset, autosomal‐recessive juvenile parkinsonism (AJRP), presumably as a result of a lack of function that alters the level, activity, aggregation or localization of its substrates. Recently, we have reported that phospholipase Cγ1 is a substrate for parkin. In this article, we show that parkin mutants and siRNA parkin knockdown cells possess enhanced levels of phospholipase Cγ1 phosphorylation, basal phosphoinositide hydrolysis and intracellular Ca2+ concentration. The protein levels of Ca2+‐regulated protein kinase Cα were decreased in AJRP parkin mutant cells. Neomycin and dantrolene both decreased the intracellular Ca2+ levels in parkin mutants in comparison with those seen in wild‐type parkin cells, suggesting that the differences were a consequence of altered phospholipase C activity. The protection of wild‐type parkin against 6‐hydroxydopamine (6OHDA) toxicity was also established in ARJP mutants on pretreatment with dantrolene, implying that a balancing Ca2+ release from ryanodine‐sensitive stores decreases the toxic effects of 6OHDA. Our findings suggest that parkin is an important factor for maintaining Ca2+ homeostasis and that parkin deficiency leads to a phospholipase C‐dependent increase in intracellular Ca2+ levels, which make cells more vulnerable to neurotoxins, such as 6OHDA.