A new article published in the Journal of Investigative Dermatology reported that Jun N-terminal kinase (JNK) is involved in inflammasome activation in myeloid immune cells. This article elaborated on a study which showed p38 MAPK is required for inflammasome activation and interleukin (IL)-1β secretion in primary human keratinocytes. This study used selective small molecule inhibitors, small interfering RNA (siRNA) gene silencing, and CRISPR/Cas9-based deletion to demonstrate that p38 MAPK is required for inflammasome activation and interleukin (IL)-1β secretion, and to identify p38α and p38δ as critical regulators of ASC (apoptosis-associated speck-like protein with a caspase-recruitment domain) oligomerization, inflammasome activation, and IL-1β secretion in keratinocytes. The results also indicated that the nature of the MAPK regulating inflammasome activity exhibits a certain cell specificity with p38 playing an important role in keratinocytes and JNK1 in cells of myeloid origin.