TM4SF11 is only 102 kb from the chemokine gene cluster composed of SCYA22, SCYD1, and SCYA17 on chromosome 16q13. CKLF maps on chromosome 16q22. CKLFs have some characteristics associated with the CCL22/MDC, CX3CL1/fractalkine, CCL17/TARC, and TM4SF proteins. Bioinformatics based on CKLF2 cDNA and protein sequences in combination with experimental validation identified eight novel genes designated chemokine-like factor superfamily members 1-8 (CKLFSF1-8). CKLFSF1-8 form gene clusters; the sequence identities between CKLF2 and CKLFSF1-8 are from 12.5 to 39.7%. Most of the CKLFSFs have alternative RNA splicing forms. CKLFSF1 has a CC motif and higher sequence similarity with chemokines than with any of the other CKLFSFs. CKLFSF8 shares 39.3% amino acid identity with TM4SF11. CKLFSF1 links the CKLFSF family with chemokines, and CKLFSF8 links it with TM4SF. The characteristics of CKLFSF2-7 are intermediate between CKLFSF1 and CKLFSF8. This indicates that CKLFSF represents a novel gene family between the SCY and the TM4SF gene families.