PLEKHF1 and mood disorder: Piechota et al. (2010) revealed that 42 drug-responsive genes in the striatum cluster into two gene expression patterns with Plekhf1 identified in the first sub-cluster of the second pattern that shows an early response to ethanol, morphine, and heroin. In another study, Plekhf1 was upregulated by both morphine and heroin and is associated with psychological dependence to these drugs (Wu et al., 2018). Thus, ample evidence exists for an important role of the Plekhf1 gene in stress-related behavioral effects, mood disorders, and substance use.