In the cytoplasm of resting neutrophils (1), the conformation of p47^phox renders cryptic its SH3 and PX domains, regions that have the potential to interact with targets on the phagosomal or plasma membrane. TNFα-mediated activation of p38/ERK (1/2) phosphorylates ³⁴⁵S in the autoinhibitory region (AIR) of p47^phox (2), allowing the prolyl isomerase Pin1 to bind and catalyze a conformational change in p47^phox (3), with subsequent phosphorylation of neighboring serines by protein kinase C (PKC). Now revealed after Pin1-induced conformational rearrangement, SH3 domains of p47^phox can associate with the membrane-bound p22^phox and complete the assembly and activation of the NADPH oxidase (5). See the complete figure in the article beginning on page 5795.