Preheat oven to 375°F and grease a 2-quart baking dish.
Bring a large pot of salted water to boil and blanch cauliflower florets for 5 minutes until just tender, then drain well and arrange in the prepared baking dish.
In a medium saucepan, melt 4 tablespoons butter over medium heat, then whisk in flour and cook for 1 minute to create a roux.
Gradually whisk in milk and cook, stirring constantly, until sauce thickens, about 5 minutes.
Remove from heat and stir in cheddar cheese, garlic powder, salt, pepper, and ground mustard until cheese is melted and sauce is smooth.
Pour cheese sauce evenly over the cauliflower, then toss panko breadcrumbs with melted butter and sprinkle over the top.
Bake for 25-30 minutes until bubbly and breadcrumbs are golden brown, then let rest 5 minutes before serving.