A novel cDNA was cloned from human endometrium, matching a human gene with the interim name KIAA1463. An mRNA identified by 5′-rapid amplification of cDNA ends was found to be 3349 nt in length. PCR analysis also identified another transcript of 6626 nt, with an open reading frame encoding a 900 amino acid protein. A fold recognition program identified similarity to firefly luciferase containing an AMP-binding motif; hence, we refer to the predicted protein as the AMP binding/luciferase-like protein (ALLP). ALLP mRNA and protein were expressed throughout the female reproductive tract with the highest levels found in the ovary and uterus. In situ hybridization and immunohistochemistry showed predominant localization of the ALLP mRNA/protein in endometrial glandular epithelium and within the theca and granulosa cells in the ovary. In the endometrium expression of ALLP, mRNA and protein were higher during d 16-21 of the secretory phase of the cycle. Western blot analysis showed decreased expression of ALLP in the postmenopausal endometrium, and hormone replacement therapy increased the expression of ALLP. Endometrial adenocarcinoma cell lines expressed more ALLP, compared with cultured primary endometrial cells or normal endometrial tissue. The ubiquitous expression of ALLP in reproductive and nonreproductive tissues suggests that this protein, which is probably regulated by ovarian steroids, plays an important metabolic role and may be involved in such processes as implantation and tumorigenesis.