Extracytoplasmic function (ECF) sigma factors are a major type of bacterial signal-transducers whose biological functions remain poorly characterized in streptomycetes. In this work we studied SCO4117, a conserved ECF sigma factor from the ECF52 family overexpressed during substrate and aerial mycelium stages. The ECF52 sigma factors harbor, in addition to the ECF sigma factor domain, a zinc finger domain, a transmembrane region, a proline-rich C-terminal extension, and a carbohydrate-binding domain. This class of ECF sigma factors is exclusive to Actinobacteria. We demonstrate thatSCO4117is an activator of secondary metabolism, aerial mycelium differentiation, and sporulation, in all the culture media (sucrose-free R5A, GYM, MM, and SFM) analyzed. Aerial mycelium formation and sporulation are delayed in aSCO4117knockout strain. Actinorhodin production is delayed and calcium-dependent antibiotic production is diminished, in the ΔSCO4117mutant. By contast, undecylprodigiosin production do not show significant variations. The expression of genes encoding secondary metabolism pathways (deoxysugar synthases, actinorhodin biosynthetic genes) and genes involved in differentiation (rdl, chp, nepA, ssgB) was dramatically reduced (up to 300-fold) in theSCO4117knockout. A putative motif bound, with the consensus "CSGYN-17bps-SRHA" sequence, was identified in the promoter region of 29 genes showing affected transcription in theSCO4117mutant, including one of theSCO4117promoters.SCO4117is a conserved gene with complex regulation at the transcriptional and post-translational levels and the first member of the ECF52 family characterized.