We reported in the previous Crohn’s and Colitis Congress and published in Refs 1 and 2 ,that a segment of 5 aa of a CD44 variant -Methionine, Threonine, Alanine, Aspartic Acid, Valine (MTADV), called 5-MER peptide (5MP), inhibits the inflammation in DSS and TNBS mouse models of IBD, when subcutaneously injected or orally delivered. Similarly, 5MP inhibited the inflammation in mouse models of Multiple Sclerosis (MS) and Rheumatoid Arthritis (RA; Ref 2). As IBD, MS and RA share up-regulation of pathological Serum Amyloid A (SAA) (which fuels chronic inflammations), we predicted and then showed that 5-MP targets and hampers the pathological SAA, thus ameliorating SAA-associated inflammatory diseases by inhibiting the release of pro-inflammatory cytokines from SAA-activated innate-immunity cells.