The gene encompasses approximately 100 Kb and may contain up to 7 exons. The entire protein-coding region is contained within the last exon.

Transcription is complex. Alternative spliced transcripts containing distinct combinations of 5 non-coding exons occur. Alternative promoters have been described and are proposed to mediate tissue specific expression of NRIP1. NRIP1 is induced by a number of hormone nuclear receptors including the receptors for estrogen, retinoic acid, androgen, progestins, vitamin D3, peroxisome proliferators-activated receptor-alpha (PPARalpha) and estrogen related receptor-alpha (ERRalpha). NRIP1 gene transcription is also induced by E2F transcription factors.
NRIP1 mRNA is widely expressed in various tissues and cell types.

None known.

NRIP1 consists of 1158 amino acids. NRIP1 contains ten LXXLL nuclear receptor interaction motifs and four transcriptional repression domains (RD 1-4). NRIP1 also contains four c-terminal binding protein (CtBP) interaction motifs. NRIP1 activity is regulated by a variety of posttranslational modifications including acetylation, methylation, phosphorylation, sumoylation, and pyridoxal-phosphate (PLP) conjugation.

NRIP1 is expressed at low levels in most tissues and is induced in response to hormonal signals. NRIP1 is highly expressed in metabolic and reproductive organs and tissues including the liver, adipose tissue, skeletal muscle, ovary and endometrium.

NRIP1 is mainly expressed in the nucleus and contains two putative nuclear localization signals (NLS).

NRIP1 is a co-repressor of a large number of nuclear receptors. NRIP1 interacts preferentially with ligand-bound nuclear receptors and inhibits transactivation by recruitment of histone deacetylases and CtBP. Knockout mice studies revealed that NRIP1 has a physiologic role in energy homeostasis, muscle metabolism, adipocyte and hepatocyte function, mitochondrial activity, inflammation, reproduction and cognition. Data suggest that these roles are mediated by NRIP1 repression of nuclear receptor mediated gene expression including gene expression mediated by the estrogen receptor, liver X receptor, PPARs, steroidogenic factor 1 (SF1) and ERR.
NRIP1 has been shown to regulate retinoic acid mediated differentiation and growth suppression of human embryonal carcinoma cells and the proliferation of breast cancer cells in vitro. A potential role for NRIP1 in cancer cachexia has been suggested. Interestingly, NRIP1 also regulates the activity of other transcription factors including E2Fs and NFKB.
The fact that NRIP1 expression can be regulated by multiple transcription factors and especially nuclear receptors and their ligands and that NRIP1 can inhibits the activity of multiple nuclear receptors implies a potential role in the biology of hormone-dependent cancers. This role in cancer biology which has recently been described in colon, stomach, breast and cervix.

NRIP1 is highly conserved throughout vertebrates. There is only a single isoform in humans and mice.

Several synonymous and non-synonymous SNPs have been identified. To date no somatic tumor mutations have been noted.
- Arg448Gly has been associated with endometriosis.
- Gly75Gly has been associated with male infertility.