### KIR2DL4 Gene Overview

**Gene Symbol**: KIR2DL4  
**Location**: Chromosome 19q13.4  
**Gene Type**: Protein-coding gene  
**Function**: KIR2DL4 encodes a killer immunoglobulin-like receptor that interacts with non-classical major histocompatibility class Ib molecule HLA-G and is primarily involved in regulating immune responses, particularly at the maternal-fetal interface.

### 1. Associated Genes
While the summaries provided reference specific KIR framework genes, KIR2DL4 is also associated with other immune-related genes and pathways. Notable associated genes include:

- **HLA-G**: The primary ligand for KIR2DL4; involved in immune tolerance during pregnancy.
- **ITIM genes**: Genes that encode proteins with immune tyrosine-based inhibitory motifs that may interact with KIR proteins, thus modulating inhibitory signals (potentially not directly related to KIR2DL4 but pertinent in pathways it influences).
- **PRKDC**: Involved in the pathways activated upon KIR2DL4 engagement, especially connected with DNA repair and immune signaling.
- **AKT1**: Involved in the signaling cascades activated downstream of KIR2DL4 interaction with HLA-G.

### 2. Aging and Age-Related Diseases
Research implicates that immune modulators like KIR2DL4 could have roles in aging and age-related diseases due to their influence on immune response and inflammation. Some potential associations include:

- **Cancer**: The balance between immune tolerance and anti-tumor responses in elderly individuals may be influenced by KIR2DL4, especially regarding its interactions with HLA-G expressing tumor cells.
- **Autoimmune Diseases**: Changes in KIR2DL4 expression or function might affect susceptibility to autoimmune conditions in aging populations, as these conditions often involve dysregulation of immune checkpoints.
- **Chronic Inflammation**: KIR2DL4 could contribute to inflammation and senescence, which are hallmark features of aging and are linked to various age-related diseases.

### 3. Drug Interactions
While specific pharmacological interactions with KIR2DL4 are less characterized in the literature, it is noteworthy that drugs modulating immune checkpoint pathways (such as monoclonal antibodies targeting other KIR receptors or related molecules) may indirectly influence KIR2DL4 activity. Potential classes of drugs include:

- **Immune checkpoint inhibitors**: Although primarily targeting PD-1 or CTLA-4 pathways, these agents could influence the broader immunological context that includes KIR proteins.
- **Immunosuppressants**: Medications that modify T cell activity might indirectly impact KIR2DL4-related signaling pathways.

### 4. Pathways and Biological Processes
KIR2DL4 is involved in various biological processes and signaling pathways, including:

- **Immune response regulation**: Primarily influencing natural killer cell activity and T cell function.
- **Cellular senescence**: Plays a role in the activation of senescence-associated secretory phenotypes, particularly in decidual NK cells during pregnancy.
- **Cytokine production**: Upon activation, KIR2DL4 can influence the production of pro-inflammatory cytokines via NF-kappa-B signaling.
- **Maternal-fetal tolerance**: KIR2DL4's interaction with HLA-G is critical in maintaining immune tolerance during pregnancy, thus influencing fetal development and placentation.

KIR2DL4 is a vital component of the immune system with complex roles that extend beyond its basic receptor-ligand interactions, connecting it to significant implications for health, disease, and immune regulation during aging.