### NEDD4L Gene Overview

**Gene Symbol:** NEDD4L  
**Location:** Human chromosome 18  
**Gene Type:** Protein-coding  

#### Summary Description
The NEDD4L gene encodes a member of the Nedd4 family of HECT domain E3 ubiquitin ligases, which are important for ubiquitination processes that target proteins for degradation. This gene plays critical roles in various signaling pathways, including those involved in sodium transport, TGF-beta signaling, autophagy, and innate immunity. Notably, NEDD4L is involved in regulating the epithelial sodium channel (ENaC) and contributes to the pathophysiology of essential hypertension through polymorphisms.

### 1. Associated Genes
While the summaries provided mention several specific target proteins (ENaC, TGFBR1, ULK1, ASCT2, etc.), NEDD4L is also associated with the following genes:
- **NTRK1:** NEDD4L ubiquitinates NTRK1 following stimulation by NGF (nerve growth factor), impacting neuron signaling.
- **TRAF3:** An important regulator in the immune responses, known to be ubiquitinated by NEDD4L, particularly influencing antiviral immunity.
- **SGK1 and TNK2:** Ubiquitination of these genes suggests a role in growth factor and survival signaling.
- **CAV1:** Caveolin-1, which may be involved in the endocytic process that affects membrane trafficking.

### 2. Aging and Age-Related Diseases
While specific direct associations with aging are scant, the role of NEDD4L in cellular processes such as autophagy and signaling pathways may have implications for age-related conditions. Altered ubiquitin-proteasome function is often linked to senescence, neurodegenerative diseases, and cancer. Research suggests that NEDD4L may influence the stability of important proteins tied to these processes. Its regulation of TGF-beta signaling is particularly relevant in fibrosis and other age-related diseases such as cardiovascular issues and cancer progression.

### 3. Drug Interactions
Currently, there are no specific drugs directly targeting NEDD4L that are widely recognized. However:
- **Ubiquitin-proteasome pathway inhibitors:** Gaining attention in cancer therapy, these may indirectly affect NEDD4L’s functions by altering the overall ubiquitin environment.
- **Antiviral agents:** Since NEDD4L plays a role in antiviral immune responses, drugs that enhance innate immunity may indirectly interact with NEDD4L’s function, although specific interactions are not well-documented.

### 4. Pathways and Biological Processes
NEDD4L is involved in several critical biological pathways:
- **Ubiquitin-mediated proteolysis:** Specifically, it is implicated in the polyubiquitination and degradation of various substrates.
- **Regulation of epithelial sodium transport:** Through ENaC, influencing fluid balance and blood pressure.
- **TGF-beta signaling regulation:** By marking SMAD2 and TGFBR1 for degradation, impacting fibrotic responses.
- **Signal transduction in innate immunity:** Particularly through the regulation of TRAF3.
- **TOR signaling regulation:** Involved in controlling cellular growth and metabolism.
- **Autophagy regulation:** Through interactions with ULK1, affecting cellular senescence and turnover processes.

Overall, NEDD4L plays a multifaceted role in cellular signaling, immune responses, and the maintenance of cellular homeostasis, with potential implications in health and disease, particularly in aging and cardiovascular health. Further research could elucidate its roles in these contexts more clearly.