The night before: Pat beef brisket dry and place in a shallow pan.
In a bowl, whisk buttermilk, hot sauce, and garlic. Pour mixture over brisket. Cover and refrigerate overnight, or up to 24 hours.
The day of: Remove brisket from marinade and allow excess to drip away.
Preheat oven to 300F.
In a small bowl, combine cayenne, brown sugar, smoked paprika, chili powder, onion powder, garlic powder, and salt and pepper to taste. Season brisket with mixture.
Place brisket fat-side down in a pan and cover tightly with foil. Transfer to oven and roast 11-12 hours.
Carefully remove brisket from oven and rest 20 minutes.
While the brisket rests, melt butter in a small saucepan. Add cayenne pepper, honey, and paprika and stir to combine.
Slice brisket and serve smothered in sauce.
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