**Core Concept**
Progressive multifocal leukoencephalopathy (PML) is a rare and often fatal demyelinating disease of the central nervous system, caused by the reactivation of the JC virus in immunocompromised individuals. The JC virus typically infects the oligodendrocytes, leading to demyelination and subsequent neurological symptoms.

**Why the Correct Answer is Right**
The JC virus is a polyomavirus that usually remains latent in the human body. In immunocompromised patients, such as those with HIV/AIDS, lymphoma, or taking immunosuppressive drugs, the JC virus can reactivate and cause PML. The virus primarily targets the oligodendrocytes, which are responsible for producing myelin, leading to demyelination and subsequent neurological symptoms. Natalizumab, a monoclonal antibody used to treat multiple sclerosis and Crohn's disease, has been associated with an increased risk of PML.

**Why Each Wrong Option is Incorrect**
**Option A:** Tacrolimus, a calcineurin inhibitor used in organ transplantation, can cause immunosuppression, but it is not the most common cause of PML.
**Option B:** Methotrexate, a chemotherapeutic agent, can also cause immunosuppression, but it is not directly linked to PML.
**Option C:** Corticosteroids, used in various inflammatory conditions, can suppress the immune system, but they are not the primary cause of PML.

**Clinical Pearl / High-Yield Fact**
Natalizumab has been associated with an increased risk of PML, particularly in patients with multiple sclerosis or Crohn's disease. It is essential to monitor patients on natalizumab for signs of PML, such as new neurological symptoms or changes in mental status.

**Correct Answer: C. Natalizumab**