The NEDD4L gene encodes a ubiquitin ligase that targets the epithelial sodium channel for degradation. A search for transcripts whose levels increase following androgen treatment of LNCaP human prostate cancer cells led to the isolation of three new NEDD4L transcripts designated NEDD4Lf, NEDD4Lg and NEDD4Lh. The three transcripts encode different forms of the NEDD4L protein, two of which contain an N-terminal C2 domain. These transcripts were detected at high levels in human prostate and mammary gland, and at lower levels in brain and skeletal muscle. We also found that the previously described NEDD4La and NEDD4Lc (KIAA0439) transcripts are also expressed in prostate and LNCaP cells. However, only NEDD4Lf, NEDD4Lg and NEDD4Lh were up-regulated by androgen in LNCaP cells. These data provide new information on the structure and expression profile of NEDD4L-derived transcripts and identify specific isoforms of the NEDD4L ubiquitin ligase as proteins with potentially important roles in androgen action and prostate physiology.