YKL-39, also known as chitinase 3-like 2, is secreted chitinase-like protein which contains Glyco_18 domain with no chitinase catalytic activity but with putative lectin properties (1, 2). In contrast to its closest homologue YKL-40, YKL-39 is not a glycoprotein. YKL-39 is secreted by articular chondrocytes, also synoviocytes (3) and activates signal-regulated kinases ERK1/ERK2 in human embryonic kidney cells (4). Increased levels of YKL-39 have been demonstrated in synovial fluids of patients with osteoarthritis (OA) or rheumatoid arthritis (RA) (5, 6) as well as in malignant tumors, particularly in glioblastomas (7). It is currently recognized as a biomarker for the activation of chondrocytes and the progress of the osteoarthritis in human (5). In addition, autoantibodies to YKL-39 were detected in 8–11.8% of patients with RA (8, 9), and 11.1% of patients with OA (9), while only 1% of patients with RA had autoantibodies to YKL-40 (8). Maturation of monocyte derived macrophages in the presence of Th2 cytokine IL-4 and TGF-beta leads to the strong activation of YKL-39 expression. Thus elevated levels of YKL-39 observed during chronic inflammations can not be attributed solely to the activity of chondrocytes. In perspective, YKL-39 is also proposed as a useful biomarker to detect macrophage-specific response in tumor, atherosclerosis and neurodegenerative diseases including Alzheimer disease, in addition to the chondrocyte-specific activation.