The cytokine interleukin-17 (IL-17) is secreted by T helper 17 (TH17) cells and is beneficial for microbial control; however, it also causes inflammation and pathological tissue remodeling in autoimmunity. Hence, TH17 cell differentiation and IL-17 production must be tightly regulated, but, to date, this has been defined only in terms of transcriptional control. Phosphatidylinositols are second messengers produced during T cell activation that transduce signals from the T cell receptor (TCR) and costimulatory receptors at the plasma membrane. Here, we found that phosphatidylinositol 4,5-bisphosphate (PIP2) was enriched in the nuclei of human TH17 cells, which depended on the kinase PIP5K1α, and that inhibition of PIP5K1α impaired IL-17A production. In contrast, nuclear PIP2 enrichment was not observed in TH1 or TH2 cells, and these cells did not require PIP5K1α for cytokine production. In T cells from people with multiple sclerosis, IL-17 production elicited by myelin basic protein was blocked by PIP5K1α inhibition. IL-17 protein was affected without altering either the abundance or stability of IL17A mRNA in TH17 cells. Instead, analysis of PIP5K1α-associating proteins revealed that PIP5K1α interacted with ARS2, a nuclear cap-binding complex scaffold protein, to facilitate its binding to IL17A mRNA and subsequent IL-17A protein production. These findings highlight a transcription-independent, translation-dependent mechanism for regulating IL-17A protein production that might be relevant to other cytokines.