Transcription factor that plays a critical role in innate immunity by activating expression of type I interferon (IFN) IFNA and INFB and inflammatory cytokines downstream of endolysosomal toll-like receptors TLR7, TLR8 and TLR9 (PubMed:15665823). Regulates the transcription of type I IFN genes (IFN-alpha and IFN-beta) and IFN-stimulated genes (ISG) by binding to an interferon-stimulated response element (ISRE) in their promoters (PubMed:15665823). Can efficiently activate both the IFN-beta (IFNB) and the IFN-alpha (IFNA) genes and mediate their induction downstream of the TLR-activated, MyD88-dependent pathway (PubMed:15665823). Maintained as a monomer in an autoinhibited state (PubMed:25326420). Phosphorylation and activation follow the following steps: innate adapter protein TASL recruits IRF5, thereby licensing IRF5 for phosphorylation by IKBKB (By similarity). Phosphorylated IRF5 dissociates from the adapter proteins, dimerizes, and then enters the nucleus to induce IFNs (PubMed:25326420). Homodimer, when phosphorylated (PubMed:25326420). Interacts with TASL (via pLxIS motif); interaction takes place downstream of TLR7, TLR8 or TLR9, leading to its activation (By similarity). Interacts with MYD88 and TRAF6 (PubMed:15665823). Shuttles between the nucleus and the cytoplasm: upon activation by the TLR adapter MYD88 and subsequent phosphorylation, translocates to the nucleus. Phosphorylation of serine and threonine residues by IKBKB in a C-terminal autoinhibitory region, stimulates dimerization, transport into the nucleus, assembly with the coactivator CBP/EP300 and initiation of transcription. 'Lys-63'-linked polyubiquitination by TRAF6 is required for activation. Mice develop normally and no overt phenotype is observed in hematopoietic cell population (PubMed:15665823). However, the induction of pro-inflammatory cytokines, such as interleukin-6 (IL6) and IL12 by various TLR ligands is impaired, whereas interferon-alpha induction is normal (PubMed:15665823). Belongs to the IRF family.