### ERFE Gene Overview 

**Gene Symbol:** ERFE  
**Function:** The ERFE gene encodes an iron-regulatory hormone that is primarily produced by erythroblasts in response to hemorrhage. This hormone plays a critical role in iron metabolism, particularly by suppressing hepcidin (HAMP) expression in the liver, which enhances iron absorption and mobilization from stores. Additionally, ERFE has regulatory roles in glucose and lipid metabolism, apoptotic processes, and inflammation.

### 1. Associated Genes

ERFE is associated with several genes, particularly those involved in metabolic processes and iron regulation. Some notable gene associations include:

- **HAMP (Hepcidin antimicrobial peptide):** A key regulator of iron homeostasis that is inhibited by ERFE.
- **IRS1 (Insulin receptor substrate 1):** Involved in insulin signaling pathways.
- **AKT (Protein kinase B):** A central player in cell survival and metabolism, particularly in the context of ERFE-mediated signaling.
- **BMP2 (Bone Morphogenetic Protein 2):** ERFE may sequester BMP2, impacting osteoblast differentiation and bone metabolism.
- **RANKL (Receptor Activator of Nuclear Factor kappa-Β Ligand):** Promotes osteoclastogenesis and is indirectly regulated due to ERFE's effects on BMP signaling.

### 2. Aging and Age-Related Diseases

While specific literature directly linking ERFE to aging or age-related diseases is limited, its role in iron metabolism, inflammation, and metabolic regulation suggests potential connections. Dysregulation of iron homeostasis has been implicated in:

- **Anemia of Aging:** Increased hepcidin levels can lead to reduced iron availability, resulting in anemia, particularly in older populations.
- **Metabolic Syndrome:** ERFE's role in glucose and lipid metabolism could implicate it in age-related metabolic disorders such as type 2 diabetes and obesity.
- **Cardiovascular Diseases:** With involvement in cardiomyocyte survival and inflammatory regulation, alterations in ERFE expression could influence age-associated cardiovascular pathologies.

### 3. Known Drug Interactions

ERFE itself may not have direct drug associations widely documented; however, its role in metabolic pathways suggests interactions with several drug classes that affect metabolism and hematopoiesis, such as:

- **Iron Supplements:** Due to its role in iron regulation, altering ERFE levels may affect the therapeutic response of iron supplements.
- **Antidiabetic Drugs:** Medications targeting insulin signaling pathways, such as metformin, can indirectly relate to ERFE functions.
- **Anti-inflammatory Drugs:** Drug classes that modulate inflammation may impact ERFE-associated signaling pathways and downstream effects.

### 4. Pathways and Biological Processes

ERFE is involved in several key biological pathways and processes:

- **Iron Homeostasis:** Negative regulation of hepcidin, promoting iron absorption.
- **Metabolic Regulation:**
  - Positive regulation of glucose transport and signaling pathways.
  - Regulation of fatty acid metabolism and transport.
- **Cell Survival and Inflammation:** Modulating AKT signaling promotes cell survival and reduces inflammatory responses, particularly in cardiomyocytes.
- **Bone Metabolism:** Regulation of osteoblast and osteoclast activity through BMP2 signaling.
- **Autophagy:** Inhibiting nutrient deficiency-induced autophagy via activation of the AKT-MTOR pathway.

### Summary

The ERFE gene plays a multifaceted role in regulating iron homeostasis, metabolic processes, and cellular responses to stress, with potential implications in aging and various diseases. Further research may elucidate its involvement in specific age-related conditions and therapeutic strategies.