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PDZ/LIM genes encode a group of proteins that play very important, but diverse, biological roles. They have been implicated in numerous vital processes, e.g., cytoskeleton organization, neuronal signaling, cell lineage specification, organ development, and oncogenesis. In mammals, there are ten genes that encode for both a PDZ domain, and one or several LIM domains: four genes of the ALP subfamily (ALP, Elfin, Mystique, and RIL), three of the Enigma subfamily (Enigma, Enigma Homolog, and ZASP), the two LIM kinases (LIMK1 and LIMK2), and the LIM only protein 7 (LMO7). Functionally, all PDZ and LIM domain proteins share an important trait, i.e., they can associate with and/or influence the actin cytoskeleton. We review here the PDZ and LIM domain-encoding genes and their different gene structures, their binding partners, and their role in development and disease. Emphasis is laid on the important questions: why the combination of a PDZ domain with one or more LIM domains is found in such a diverse group of proteins, and what role the PDZ/LIM module could have in signaling complex assembly and localization. Furthermore, the current knowledge on splice form specific expression and the function of these alternative transcripts during vertebrate development will be discussed, since another source of complexity for the PDZ and LIM domain-encoding proteins is introduced by alternative splicing, which often creates different domain combinations.

PDZ and LIM Domain-Encoding Genes: Molecular Interactions and their Role in Development