The ASYMMETRIC LEAVES2 (AS2) gene is involved in leaf development along adaxial-abaxial, medial-lateral and proximal-distal axes in Arabidopsis. The AS2 gene belongs to the AS2/LATERAL ORGAN BOUNDARIES (LOB) family. There are 42 members of the AS2/LOB family in the Arabidopsis genome. Many recent studies revealed that AS2/LOB family genes are involved in various physiological processes including the regulation of development and metabolism in plants. The approximately 100 amino acid AS2/LOB-domain, which defines this family, is highly conserved. Conserved regions include the C-motif, an internal region containing an invariant glycine residue, and a leucine-zipper-like motif, in the case of class I proteins. The conserved AS2/LOB-domain of AS2 cannot be functionally replaced by those of other members of the family. AS2 acts in a same pathway as that of AS1, which is an ortholog of ROUGH SHEATH2 of maize and PHANTASTICA of snapdragon. Recent molecular genetic studies for the role of AS2 provided important information. The regulation of gene expression and leaf development by AS2 is genetically linked with the regulations based on chromatin level, post-transcriptional level, protein metabolism and cell proliferation. These novel insights contribute to a better understanding of the role of AS2/LOB family genes for plant morphogenesis and physiological responses.