Type II acute-phase protein (APP) involved in inflammatory responses to trauma. May also play a role in liver development or regeneration. Interacts (via C-terminus) with DNAJC1 (via SANT 2 domain); this interaction protects ITIH4 against cleavage by kallikrein in vitro. Liver specific. Levels increase from 1.4 to 3-fold in acute-phase processes such as in acute ischemia stroke (AIS), unstable angina and programmed surgery. In hepatocytes, induced by IL6 but not by other cytokines such as IL1B. Cleaved by plasma kallikrein to yield 100 kDa and 35 kDa fragments, and the resulting 100 kDa fragment is further converted to a 70 kDa fragment. N- and O-glycosylated. In urine, O-linked glycosylation on threonine residues in the region from Thr-719 to Thr-725 consists of core 1 or possibly core 8 glycans. Mainly Hex(HexNAc)(2), but also some Hex(3)(HexNAc)(3). N-glycosylated but not O-glycosylated in plasma. Possible biomarker for acute ischemic stroke (PubMed:19263524). Peptides derived from the proline-rich potentially active peptide (PRO_0000016542) may be biomarkers for a variety of disease states including breast cancer (PubMed:21137033). Belongs to the ITIH family.