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AIM1 is a novel gene whose expression is associated with the experimental reversal of tumorigenicity of human malignant melanoma. The predicted protein product of the major 4.1-kb transcript shows striking similarity to the [Beta][Gamma]-crystallin superfamily. All known members of this super-family contain two or four characteristic motifs arranged as one or two symmetrical domains. AIM1, in contrast, contains 12 [Beta][Gamma] motifs, suggesting a 6-domain structure resembling a trimer of [Beta]- or [Gamma]-crystallin subunits. The structure of the AIM1 gene shows remarkable similarity to [Beta]-crystallin genes, with homologous introns delineating equivalent protein structural units. AIM1 is the first mammalian member of the [Beta][Gamma] superfamily with a primarily non-lens role. Other parts of the predicted AIM1 protein sequence have weak similarity with filament or actin-binding proteins. AIM1 is a good candidate for the putative suppressor of malignant melanoma on chromosome 6, possibly exerting its effects through interactions with the cytoskeleton.