The c-Jun N-terminal kinase (JNK) is part of a stress activated mitogen-activated protein kinase (MAPK) signaling cascade composed of MAP2K and MAP3K signaling components. Scaffold proteins are lacking enzymatic activity, simultaneously associate with various components of the MAPK signaling pathway and play a crucial role in signal transmission and regulation. A novel scaffold JNK-binding protein was isolated in our lab using the yeast Ras Recruitment System designated; WDR62. WDR62 specifically associates with JNK but not with ERK and p38. WDR62 over-expression in HeLa cells results in JNK activation that is not followed by transcription activation through the AP-1 transcription factor. Immunofluorescence analysis shows that over-expression of WDR62 in 293T cells, promotes the assembly of stress granules in transfected cells, resulting in recruitment of activated JNK to the stress granule. Recently WDR62 was found to be mutated in patients with a wide spectrum of severe cerebral cortical malformations including microcephaly and pachgyria. We sought to biochemically characterize WDR62 protein partners to reveal its biological role during normal cellular growth and in the disease state. WDR62 associates with endogenous and overexpressed proteins of both JNK2 and MKK7. These associations occur via direct protein-protein interactions. WDR62 associates with the MKK7b1 isoform independently of JNK binding. One of the WDR62 mutant proteins found in a patient with microcephaly encodes a C-terminal truncated protein that preserves both JNK and MKK7 docking domains yet fails to associate with them. The WDR62 C-terminal region, that is absent in the mutated protein, harbors a novel dimerization domain composed of three a-helices. Importantly, fusion of the WDR62 dimerization mutant to a functional heterologous dimerization motif is able to reconstitute WDR62-JNK association but not the association of MKK7. Collectively, WDR62 dimerization domain is critical for its scaffolding function.